Cd16a binding agents and uses thereof

Abstract

Among other things, the present disclosure provides compounds, compositions thereof, and methods of using the same. In some embodiments, compounds of the present disclosure bind to Fc receptors, e.g., CD16a. In some embodiments, compounds of the present disclosure are useful for treating various conditions, disorders or diseases including cancer.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Application No. 62 / 614,607, filed Jan. 8, 2018, the entirety of which is incorporated herein by reference.TECHNICAL FIELD[0002]The present disclosure encompasses technologies for modulating immune activities, e.g., for treatment of various conditions, disorders or diseases. In some embodiments, the present disclosure relates to compounds and methods useful as enhancing activities of antibodies, e.g., monoclonal antibodies. In some embodiments, the disclosure also provides pharmaceutically acceptable compositions comprising provided compounds and methods of using said compositions in the treatment of various conditions, disorders or diseases, e.g., various cancers.BACKGROUND[0003]The search for new therapeutic agents has been greatly aided in recent years by the discovery and development of monoclonal antibody therapeutic agents. Several of such agents elicit their therapeutic effect thr...

AI Technical Summary

Benefits of technology

[0004]Many immune activities involve recruitment of immune cells (e.g., NK cells) to damaged, diseased, and / or defective cells (e.g., cancer cells), tissues (e.g., tumors, certain wounds, etc.), foreign objects and / or entities (e.g., infectious agents), etc. Among other things, the present disclosure provides technologies, e.g., compounds, compositions, methods, etc., that are particularly useful for triggering, generating, encouraging, and / or enhancing recruitment of immune cells to their target sites, which, among other things, can provide improved biological effects (e.g., improved therapeutic effects, lower toxicity, fewer / less severe side effects, etc.

[0005]In some embodiments, the present disclosure provides technologies that can modulate activities of certain Fc receptors. In some embodiments, the present disclosure provides compounds that can bind certain Fc receptors and compositions and methods thereof. In some embodiments, provided technologies can trigger, generate, encourage and / or enhance one or more immune activities by enhanced recruitment of immune cells that express such Fc receptors. In some embodiments, provided technologies utilize binding moieties to enhance binding to Fc receptors. In some embodiments, this approach allows for enhanced binding of antibodies, e.g., monoclonal antibodies, to Fc receptors. Among other things, such enhanced binding can provide enhanced recruitment of immune cells expressing such Fc receptors and provide improved biological results, e.g., improved therapeutic effects, lower toxicity, fewer / less severe side effects, etc.

[0008]Among other things, the present disclosure provides MATEs™ (monoclonal antibody therapeutic enhancers) technologies that can enhance desired immune responses of a subject, e.g., a patient. In some embodiments, by covalently linking the CD16a small molecule ligands of the present disclosure to antibodies, e.g., mAbs, benefits such as, for example, enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) activity can be achieved. Among other things, the MATEs (monoclonal antibody therapeutic enhancers) platform comprises the provision of compounds comprising two distinct segments: 1) an antibody, e.g., a monoclonal antibody, and 2) a binding moiety that enhances binding to receptors expressed on immune cells, e.g., CD16a. These enhanced antibodies can be prepared using a wide variety of antibodies, e.g., mAbs and binding moieties, thereby allowing tremendous versatility to address various diseases.

Problems solved by technology

Without the intention to be limited by any theory, Applicant recognizes that such less effective interactions may lead to less effective recruitments of immune cells expressing CD16a (e.g., NK cells) and / or reduced therapeutic effects (e.g., in heterozygous or homozygous subjects expressing a low-affinity form).

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